Compositions and methods for inhibition of ito as treatment for the j wave syndromes and hypothermia

Abstract

Compositions and methods for treating J Wave Syndromes via ion-channel specific and cardio-selective inhibition of Ito are disclosed. In certain embodiments, the method includes administering a composition comprising ARumenamide-787 (AR-787) to a subject.

1 . A method for treating a J Wave Syndrome (JWS) in a patient in need thereof, comprising administering an effective amount of at least one I TO  inhibitor or I NA  augmentor. 
     
     
         2 . The method of  claim 1  wherein the JWS is Brugada syndrome (BrS) or early repolarization syndrome (ERS). 
     
     
         3 . The method of  claim 1 , wherein the at least one I TO  inhibitor or I NA  augmentor is selected from Table 1. 
     
     
         4 . The method of  claim 1 , wherein the at least one I TO  inhibitor is Arumenamide-787 (AR-787). 
     
     
         5 . The method of  claim 1 , wherein treatment
 a) effectively suppresses the electrocardiogramd/or arrhythmic manifestations of JWS,   b) reduces instances of ventricular fibrillation or sudden cardiac death compared to an untreated control, or   c) reduces the amplitude of J waves when compared to an untreated control.   
     
     
         6 - 7 . (canceled) 
     
     
         8 . The method of  claim 1 , wherein at least one I TO  inhibitor and/or I NA  augmentor is administered via enteral, parenteral, topical, or pulmonary administration. 
     
     
         9 . The method of  claim 1 , further comprising administering an I CA  augmentor, a β-adrenergic agonist, quinidine, bepridil, or denopamine. 
     
     
         10 . The method of  claim 9 , wherein the I CA  augmentor is isoproterenol, cilostazol and/or milrinone. 
     
     
         11 - 12 . (canceled) 
     
     
         13 . The method of  claim 1 , wherein the patient has hypothermia. 
     
     
         14 . The method of  claim 13 , wherein the hypothermia is mild hypothermia, moderate hypothermia, severe hypothermia, or therapeutic hypothermia. 
     
     
         15 . A method for ameliorating symptoms of a J Wave Syndrome (JWS) phenotype in a patient having hypothermia, comprising administering an effective amount of at least one I TO  inhibitor or I NA  augmentor. 
     
     
         16 . The method of  claim 15 , wherein the hypothermia is mild hypothermia, moderate hypothermia, severe hypothermia, or therapeutic hypothermia. 
     
     
         17 . The method of  claim 15 , wherein the at least one I TO  inhibitor or I NA  augmentor is selected from Table 1. 
     
     
         18 . The method of  claim 15 , wherein the at least one I TO  inhibitor is Arumenamide-787 (AR-787). 
     
     
         19 . The method of  claim 15 , wherein treatment
 a) effectively suppresses the electrocardiographic or arrhythmic manifestations of JWS,   b) reduces instances of ventricular fibrillation or sudden cardiac death compared to an untreated control, or   c) reduces the amplitude of J waves when compared to an untreated control.   
     
     
         20 - 21 . (canceled) 
     
     
         22 . The method of  claim 15 , wherein at least one I TO  inhibitor and/or I NA  augmentor is administered via enteral, parenteral, topical, or pulmonary administration. 
     
     
         23 . The method of  claim 15 , further comprising administering an I CA  augmentor, a one β-adrenergic agonist, quinidine, bepridil, or denopamine. 
     
     
         24 . The method of  claim 15 , wherein the I CA  augmentor is isoproterenol, cilostazol and milrinone. 
     
     
         25 - 26 . (canceled) 
     
     
         27 . The method of  claim 15 , further comprising treating the hypothermia. 
     
     
         28 . The method of  claim 15 , wherein treating the hypothermia comprises at least one of wrapping the patient in blankets, administering warm fluids by mouth, immersing the patient in a warm water bath, and direct warming of a patient's blood.